Bone marrow stem cell (BMSC) therapy holds promise for patients suffering from heart disease. Although clinical trials have begun, basic understanding of BMSC biology remains limited. This proposal investigates BMSC therapy using murine models of ischemic heart disease. In Aim 1, BMSCs constitutively expressing molecular imaging reporter genes will be transplanted into normal myocardium to assess survival by noninvasive imaging. In Aim 2, we will define the therapeutic efficacy of these cells by transplantation into acute and chronic models of ischemic heart disease, followed by multi-modality assessment of cardiac function. In Aim 3, we will investigate the mechanisms by which BMSCs engraft, differentiate, and respond to host myocardium by gene expression profiling of BMSCs transplanted into acute and chronic ischemic cardiac milieus. The overall significance of this project is two-fold: (1) to define the survival kinetics of BMSCs in vivo and (2) to understand the mechanisms by which BMSC therapy can induce functional improvement. [unreadable] [unreadable] [unreadable]